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动脉壁中胆固醇瞬态掺入的实验测定与数学模型

Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall.

作者信息

Neumann S J, Berceli S A, Sevick E M, Lincoff A M, Warty V S, Brant A M, Herman I M, Borovetz H S

机构信息

Department of Surgery, University of Pittsburgh School of Medicine, PA 15261.

出版信息

Bull Math Biol. 1990;52(6):711-32. doi: 10.1007/BF02460805.

DOI:10.1007/BF02460805
PMID:2279192
Abstract

Experimental data of the radial incorporation of labeled cholesterol [14C-4] into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfused in vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of [14C-4] activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity, D and solute filtration velocity, V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work.

摘要

将标记胆固醇[14C - 4]径向掺入动脉壁的实验数据与一个预测该生物系统中大分子转运的数学模型进行回归分析。数据是使用在体外搏动血流动力学条件下灌注2小时的切除犬颈动脉获得的。血管分别暴露于正常血压血流动力学、高血压血流动力学或故意改变血流速率或血管顺应性的模拟条件下。在球囊导管去内皮后,对几条动脉在正常血压条件下进行研究。通过对灌注血管纵向切片进行微晶切片术来确定[14C - 4]活性的跨壁浓度分布。对12个实验病例进行非线性Marquardt回归,得出有效扩散系数D和溶质过滤速度V的参数估计值。本实验研究结果支持我们的假设,即血流动力学和内皮衬里影响完整血管中的壁通量。暴露于改变的(与正常血压相比)血流动力学与标记胆固醇掺入增加有关。对于去内皮的血管也有类似的观察结果(例如标记物积累增加和对流通量增加)。基于我们在血流动力学模拟过程中对血管壁力和内皮细胞形态的伴随测量,我们认为血流动力学诱导的内皮结构改变导致了我们在这项工作中观察到的通透性增加、对流增加和掺入增加。

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引用本文的文献

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Cholesterol Homeostasis: An In Silico Investigation into How Aging Disrupts Its Key Hepatic Regulatory Mechanisms.胆固醇稳态:关于衰老如何破坏其关键肝脏调节机制的计算机模拟研究。
Biology (Basel). 2020 Sep 30;9(10):314. doi: 10.3390/biology9100314.

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